Integrated analysis of DNA methylation profiling and gene expression profiling identifies novel markers in lung cancer in Xuanwei, China.
Integrated analysis of DNA methylation profiling and gene expression profiling identifies novel markers in lung cancer in Xuanwei, China.
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DNA 甲基化谱和基因表达谱的综合分析确定了中国宣威肺癌的新标志物
DOI：
10.1371/journal.pone.0203155
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Wang J;Duan Y;Meng QH;Gong R;Guo C;Zhao Y;Zhang Y
背景：DNA甲基化异常在癌症中经常发生。本研究的目的是通过整合全基因组DNA甲基化和基因表达研究，在中国宣威肺癌中寻找新的甲基化标记。方法采用甲基化DNA免疫沉淀结合基因芯片技术(MeDIP-CHIP)和基因表达芯片技术，分别检测10例配对肺癌组织和10例非癌肺组织的差异甲基化区域(DMRS)和差异表达基因(DEG)。对DMRS和DEGS进行整合分析，筛选出甲基化相关候选基因。进一步验证和分析了候选基因的甲基化和表达变化。结果与正常肺组织相比，肺癌组织共表达6899个DMR，包括5788个高甲基化区域和1111个低甲基化区域。DMR和DEGS的综合分析确定了45个肿瘤特异性候选基因：38个DMR高甲基化而表达下调的基因，7个DMR低甲基化而表达上调的基因。甲基化和表达验证结果确定了4个候选基因(STXBP6、BCL6B、FZD10和HSPB6)在大多数肿瘤组织中显著高甲基化，与非癌肺组织相比下调。结论通过对宣威地区肺癌全基因组DNA甲基化和基因表达的综合分析，揭示了一些在肺癌中未见报道的启动子甲基化调控基因。这些结果为宣威肺癌的发病机制提供了新的认识，为肺癌的诊断和治疗提供了新的靶点。
Background Aberrant DNA methylation occurs frequently in cancer. The aim of this study was to identify novel methylation markers in lung cancer in Xuanwei, China, through integrated genome-wide DNA methylation and gene expression studies. Methods Differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were detected on 10 paired lung cancer tissues and noncancerous lung tissues by methylated DNA immunoprecipitation combined with microarray (MeDIP-chip) and gene expression microarray analyses, respectively. Integrated analysis of DMRs and DEGs was performed to screen out candidate methylation-related genes. Both methylation and expression changes of the candidate genes were further validated and analyzed. Results Compared with normal lung tissues, lung cancer tissues expressed a total of 6,899 DMRs, including 5,788 hypermethylated regions and 1,111 hypomethylated regions. Integrated analysis of DMRs and DEGs identified 45 tumor-specific candidate genes: 38 genes whose DMRs were hypermethylated and expression was downregulated, and 7 genes whose DMRs were hypomethylated and expression was upregulated. The methylation and expression validation results identified 4 candidate genes (STXBP6, BCL6B, FZD10, and HSPB6) that were significantly hypermethylated and downregulated in most of the tumor tissues compared with the noncancerous lung tissues. Conclusions This integrated analysis of genome-wide DNA methylation and gene expression in lung cancer in Xuanwei revealed several genes regulated by promoter methylation that have not been described in lung cancer before. These results provide new insight into the carcinogenesis of lung cancer in Xuanwei and represent promising new diagnostic and therapeutic targets.
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影响因子：
3.7
作者：
Matsushima-Nishiwaki R;Toyoda H;Nagasawa T;Yasuda E;Chiba N;Okuda S;Maeda A;Kaneoka Y;Kumada T;Kozawa O
通讯作者：
Kozawa O
影响因子：
6.6
作者：
Bjaanæs MM;Fleischer T;Halvorsen AR;Daunay A;Busato F;Solberg S;Jørgensen L;Kure E;Edvardsen H;Børresen-Dale AL;Brustugun OT;Tost J;Kristensen V;Helland Å
通讯作者：
Helland Å
影响因子：
8
作者：
Fukukawa, C.;Nagayama, S.;Katagiri, T.
通讯作者：
Katagiri, T.
影响因子：
3.7
作者：
Bind, Marie-Abele;Lepeule, Johanna;Schwartz, Joel
通讯作者：
Schwartz, Joel
影响因子：
--
作者：
Li X;Yu J;Brock MV;Tao Q;Herman JG;Liang P;Guo M
通讯作者：
Guo M